Over the past several years our mouse genetics unit has isolated more than a dozen distinct recessive developmental lethal mutants of the mouse. Most of these involve mutations in the proximal region of murine chromosome 17. One, with a dominant phenotype of multiple intestinal neoplasia, lies in the murine Apc gene, a homolog of the human gene in which mutants predispose to adenomatous polyposis of the colon. This mutation, Min, is a nonsense codon within the Apc gene, is also a developmental lethal when homozygous. We are presented with a unique opportunity to investigate the extent to which developmental lesions can lead to neoplastic transformation in combination with other genetic or environmental factors. Formally, any gene for which a loss of function contributes to neoplastic transformation is classified as a "tumor suppressor gene". Our preliminary studies have identified genetic factors that modify the severity of the multiple intestinal neoplasia caused by the Min mutation. These factors include alleles of inbred mouse strains that confer a dominant relative resistance to the action of Min. Formally, such modifier loci are classified as "second-site suppressor genes". With Min we are therefore in a unique position to identify genetic factors, including transgenes encoding cytokines, that serve as second-site suppressors, or as enhancers, of the formation or growth of the class of neoplasms that is predisposed by Min. The emergent power of the genetic and physical maps of the mouse genome permit the molecular identification of genetic factors that are identified by mutant phenotype. We shall gain concrete information on whether factors that impact neoplastic transformation also control mitotic cycling in the animal.